The investigation is designed to understand how the biosynthesis of cholesterol is controlled in man such that this particular structural entity and not some other polycyclic isopentenoid is produced by the mevalonate pathway. Major biosynthetic choices have to be made. Two of these, (a) the cyclization of squalene-oxide to lanosterol vs. cyclization to cycloartenol, or to beta-amyrin, etc., and (b) the metabolism of the delta 24-bond yielding either a reduced or alkylated side chain, as in cholesterol vs. sitosterol, are to be the focal point of the study. Enzymatic, kinetic, and structural methodology will be used in cell-free systems as well as in vivo with rats or other appropriate organism to study the mechanism and consequences of these reactions. The results of the work will shed further light on normal physiology and its evolution, especially the evolution of the nervous system, as well as on metabolic abnormalities giving rise to disease (lipodoses).